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Steven Raman: Thanks, Tom. Yeah I mean, this is, lightning round MRI. I think MRI really is still—I think a meeting like this, it's sort of hard to understand where MRI fits in, but it’s still the mainstay for any sort of prostate imaging, especially in the early stage.

So we’re going to talk about MRI and really talk about where we think about MRI in 2025. And there are a lot of things we could talk about, but really the bottom line for us is based on these trials, a PIVOT trial 12 years ago, 13 years ago, showing how do we individualize care for any given patient? Because obviously there’s a lot of overtreatment based on just sort of a one-size-fits-all approach.

And I think MR is the first step to understanding who has aggressive disease and who doesn’t, and the PSMA of course, adds to that. And the PROTECT trial also shows more recently, the PROTECT trial also shows that we really have to do a better job of understanding who needs this radical therapy, who needs some lower level of therapy, and who needs active surveillance.

So for all that, I think we think about prostate cancer as minnows and sharks. In some ways, only 14% of men diagnosed with prostate cancer will progress to metastases. So in the early stage—we’re not talking about later, we’re talking about early when you are faced with this diagnosis of prostate cancer, how do you counsel people, men, about what to do? 50% of low-risk disease and most are overtreated.

So it’s a range of diseases. We need to find the minnows from the sharks. And I think that’s where I think MR, PSMA, and other modalities in the early stage will give us that understanding. And Dr. Walsh himself said many years ago, and he practiced in the era before imaging, that imaging would have the most important development in the field of—in urology and neuroradiology and the prostate.

And we used to say that prostate cancer care was blind when we were trying to implement MR and understanding where MR was. But now MR, with its multiple techniques—T2, diffusion, perfusion—with the addition of PET and PET/MR gives us this idea of understanding the whole gland and what’s happening in the gland better than anything else that we can find right now.

We can then do targeted biopsy and then do potentially focal therapy. There are many, many—this is a partial list of what MR is being used for in a very sustained fashion—detection, biopsy planning, active surveillance, surgical planning, radiotherapy planning, partial gland therapy planning, follow-up rising PSA (which is now the domain of PSMA and other agents), and then really detecting the most aggressive prostate cancer and understanding the biology of prostate cancer. So, again, some have said that up to two million men have undergone treatment unnecessarily because of the lack of this early stage understanding of prostate cancer.

So we know MRI detects up to 80% of clinically significant prostate cancer. Well we can argue about what that means. But based on our work and the work of others, and based on these very careful matching of MRI to the whole-mount histopathology cohorts, we can say that up to 80% of clinically significant prostate cancer is detected by MR.

We also know the combination—with work of Ida and others here, the work of—the combination of MRI and PSMA PET/CT are the best single—two best modalities to detect prostate cancer, and the two together do a better job than either alone. And detect almost 90% of clinically significant prostate cancer. And that’s been shown in these two papers and other papers. But these two papers that rely on whole-mount histopathology, showing that PSMA and MR parameters detect the most aggressive prostate cancers.

We also know that—we’ve used this now, and with the work of Shyam and Alan here, this is the first paper that looked at combining the MR to get the biopsy and get the most aggressive prostate cancer here. In this paper, it was the first time we actually used a UCLA score, a five-point score, which then led to PI-RADS. And since then, with MR, PI-RADS has morphed into an active surveillance-based cohort, and that’s called PRECISE. It’s morphed into a radiation therapy-based reporting system called PI-RR.

So we’re using these segmented, very specific tools for understanding these different areas of need. It’s also been now proposed to have different scoring systems—a PI-FAB and a target scores—for follow-up of focal therapy. So in our reports—when we do MR in 2025—we’re using five different scoring systems depending on what the use case is for giving our customers or referrers and ourselves an understanding of how the disease biology behaves.

So with the work of Alan and Shyam here in the audience, we were able to find the shark. We did this ourselves with MR-guided biopsy, where this patient, for example, had been biopsied four times with negative prior biopsies, four negative prior biopsies, and with the MR we can find the shark here anteriorly and find this PI-RADS 5 lesion, and then biopsy it—biopsy with MR guidance, and this can be done in many different ways.

So we showed that with that we can detect. When we say it’s a PI-RADS 5, those are very, very aggressive prostate cancers. We can also show that the MR biopsy predicts—hopefully eliminates the need for the systematic bias, because most of the systematic biopsies are in the region of the MR-targeted biopsy, and we’ve shown that with the work of Wayne and other people here.

And this is also true for PSMA. So we’re now using PSMA to biopsy these sharks. This hopefully avoids things like this—saturation biopsy—which is, I’m going to get rid of this slide because it’s pretty scary, but that’s still being done in many places.

We’ve improved surgical planning, helped surgeons plan better with MR. That’s been shown a long time. We are now using MR for things like this. This is a Tulsa and other local therapies for prostate cancer. There’s MR-guided therapy. Using MR, maybe you confuse it with PSMA and just treat with a variety of things—just the cancers or a margin around the cancers if we can find a better way to do that, and that’s still an area of need, how to find the better cancers.

So we can say that MR detects—MR and PSMA both detect the most aggressive cancers. MR visibility confers a distinct disadvantage. When you see MR-occult cancers, they behave in a different way than MR-visible cancers. We can say that we know that MR-visible cancers have different genomic and proteomic signatures, and we’ve shown that here, and we can say that this concept of nimbosus, which was coined by Dr. Paul Boutros, says that MR-visible cancers—and probably by extension PSMA—have a nimbosus concept. They’re polyclonal, hypoxic, unstable, and so on.

So they have different genomic and proteomic alterations than MR-invisible cancers. And that’s also been shown in PSMA expression. Cancers that express PSMA—low PSMA expression leads to resistance to androgen and radiation. So they’re a distinct subtype of bad cancers and predict bad biology.

So, in summary, I think MR is here to stay. It is proliferated in so many ways, and I can’t think of a single thing in prostate cancer that’s made such a difference for men who are initially faced with a prostate cancer diagnosis, helps localize the sharks, biopsy the most suspicious areas, and predict the biology in ways we’re only beginning to understand.